Nα-alkylated derivatives of 2-phenylhistamines: Synthesis and in vitro activity of potent histamine H1-receptor agonists

New potent Nα-alkylated histamine H1-receptor agonists have been prepared and functionally evaluated for partial agonist potency and selectivity. Nα-Methyl-2-(3-trifluoromethylphenyl)histamine contracts ileal segments and aortic rings of guinea-pig with a relative potency of 174% (95% confid. lim. 161 – 188%) and 217% (164 – 287%), respectively (histamine: 100%) and is the most potent H1 receptor agonist described so far.